1,578 research outputs found

    Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer

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    Kinases are signalling proteins which have proven to be successful targets for the treatment of a variety of diseases, predominantly in cancers. However, only a small proportion of kinases (<20%) have been investigated for their therapeutic viability, likely due to the lack of available chemical tools across the kinome. In this work we describe initial efforts in the development of a selective chemical tool for protein kinase N2 (PKN2), a relatively unexplored kinase of interest in several types of cancer. The most successful compound, 5, has a measured IC50 of 0.064 μM against PKN2, with ca. 17-fold selectivity over close homologue, PKN1

    Modifying the Interface Edge to Control the Electrical Transport Properties of Nanocontacts to Nanowires

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    Selecting the electrical properties of nanomaterials is essential if their potential as manufacturable devices is to be reached. Here, we show that the addition or removal of native semiconductor material at the edge of a nanocontact can be used to determine the electrical transport properties of metal-nanowire interfaces. While the transport properties of as-grown Au nanocatalyst contacts to semiconductor nanowires are well-studied, there are few techniques that have been explored to modify the electrical behavior. In this work, we use an iterative analytical process that directly correlates multiprobe transport measurements with subsequent aberration-corrected scanning transmission electron microscopy to study the effects of chemical processes that create structural changes at the contact interface edge. A strong metal-support interaction that encapsulates the Au nanocontacts over time, adding ZnO material to the edge region, gives rise to ohmic transport behavior due to the enhanced quantum-mechanical tunneling path. Removal of the extraneous material at the Au-nanowire interface eliminates the edge-tunneling path, producing a range of transport behavior that is dependent on the final interface quality. These results demonstrate chemically driven processes that can be factored into nanowire-device design to select the final properties

    Tracing the Mass during Low-Mass Star Formation. II. Modelling the Submillimeter Emission from Pre-Protostellar Cores

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    We have modeled the emission from dust in pre-protostellar cores, including a self-consistent calculation of the temperature distribution for each input density distribution. Model density distributions include Bonnor-Ebert spheres and power laws. The Bonnor-Ebert spheres fit the data well for all three cores we have modeled. The dust temperatures decline to very low values (\Td \sim 7 K) in the centers of these cores, strongly affecting the dust emission. Compared to earlier models that assume constant dust temperatures, our models indicate higher central densities and smaller regions of relatively constant density. Indeed, for L1544, a power-law density distribution, similar to that of a singular, isothermal sphere, cannot be ruled out. For the three sources modeled herein, there seems to be a sequence of increasing central condensation, from L1512 to L1689B to L1544. The two denser cores, L1689B and L1544, have spectroscopic evidence for contraction, suggesting an evolutionary sequence for pre-protostellar cores.Comment: 22 pages, 9 figures, Ap. J. accepted, uses emulateapj5.st

    NGC 7582: The Prototype Narrow-Line X-ray Galaxy

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    NGC 7582 is a candidate prototype of the Narrow Line X-ray Galaxies (NLXGs) found in deep X-ray surveys. An ASCA observation shows the hard (> 3 keV) X-ray continuum of NGC 7582 drops 40% in ~6 ks, implying an AGN, while the soft band (< 3 keV) does not drop in concert with the hard continuum, requiring a separate component. The X-ray spectrum of NGC 7582 also shows a clear 0.5-2 keV soft (kT = 0.8 (+0.9,-0.3) keV or Gamma = 2.4 +/- 0.6; L(X) = 6 x 10**40 ergs s**-1) low--energy component, in addition to a heavily absorbed [N(H) = (6 +/- 2)\times 10**22 cm**-2 ] and variable 2-10 keV power law [Gamma = 0.7 (+0.3,-0.4); L(X) = (1.7-2.3) x 10**42 ergs s**-1]. This is one of the flattest 2-10 keV slopes in any AGN observed with ASCA. (The ROSAT HRI image of NGC 7582 further suggests extent to the SE.) These observations make it clear that the hard X-ray emission of NGC 7582, the most "narrow-line" of the NLXGs, is associated with an AGN. The strong suggestion is that all NLXGs are obscured AGNs, as hypothesized to explain the X-ray background spectral paradox. The separate soft X-ray component makes NGC 7582 (and by extension other NLXGs) detectable as a ROSAT source.Comment: text: Latex2e 10 pages, including 1 table, and 2 postscript figures via psfi

    Critical perspectives on ‘consumer involvement’ in health research: epistemological dissonance and the know-do gap

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    Researchers in the area of health and social care (both in Australia and internationally) are encouraged to involve consumers throughout the research process, often on ethical, political and methodological grounds, or simply as ‘good practice’. This paper presents findings from a qualitative study in the UK of researchers’ experiences and views of consumer involvement in health research. Two main themes are presented in the paper. Firstly, we explore the ‘know-do gap’ which relates to the tensions between researchers’ perceptions of the potential benefits of, and their actual practices in relation to, consumer involvement. Secondly, we focus on one of the reasons for this ‘know-do gap’, namely epistemological dissonance. Findings are linked to issues around consumerism in research, lay/professional knowledges, the (re)production of professional and consumer identities and the maintenance of boundaries between consumers and researchers

    Engaging Communities in Sulawesi Island, Indonesia: A Collaborative Approach to Modelling Marine Plastic Debris through Open Science and Online Visualization

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    Marine litter poses a complex challenge in Indonesia, necessitating a well-informed and coordinated strategy for effective mitigation. This study investigates the seasonality of plastic concentrations around Sulawesi Island in central Indonesia during the monsoon-driven wet and dry seasons. By using open data and methodologies including the HYCOM and Parcels models, we simulated the dispersal of plastic waste over three months during both the southwest and northeast monsoons. Our research extended beyond data analysis, as we actively engaged with local communities, researchers, and policymakers through a range of outreach initiatives, including the development of a web application to visualize model results. Our findings underscore the substantial influence of monsoon-driven currents on surface plastic concentrations, highlighting the seasonal variation in the risk to different regional seas. This study adds to the evidence provided by coarser resolution regional ocean modelling studies, emphasizing that seasonality is a key driver of plastic pollution within the Indonesian archipelago. Inclusive international collaboration and a community-oriented approach were integral to our project, and we recommend that future initiatives similarly engage researchers, local communities, and decision-makers in marine litter modelling results. This study will work to support in the application of model results in solutions to the marine litter problem
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